5-Oxa-13,14-didehydro-11-deoxy-PGE1 compounds

ABSTRACT

This invention comprises certain analogs of the prostaglandins in which the double bond between C-13 and C-14 is replaced by a triple bond. Also provided in this invention, are novel chemical processes and novel chemical intermediates useful in the preparation of the above prostaglandin analogs. These prostaglandin analogs exhibit prostaglandin-like activity, and are accordingly useful for the same pharmacological purposes as the prostaglandins. Among these purposes are blood pressure lowering, labor induction at term, reproductive-cycle regulation, gastric antisecretory action, and the like.

The present application is a divisional application of Ser. No. 657,740,filed Feb. 13, 1976, now pending issuance as a U.S. patent.

The present invention relates to prostaglandin analogs, for which theessential material constituting disclosure therefor is incorporated byreference here from Ser. No. 820,974, filed Aug. 1, 1977, now U.S. Pat.No. 4,099,015, issued July 4, 1978, which is a divisional application ofSer. No. 657,740.

I claim:
 1. A prostaglandin analog of the formula ##STR1## wherein D is##STR2## wherein Z₄ is

    --CH.sub.2 --O--CH.sub.2 --(CH.sub.2).sub.g --CH.sub.2 --,

    --(ch.sub.2).sub.2 --o--(ch.sub.2).sub.g --CH.sub.2 --, or

    --(CH.sub.2).sub.3 --O--(CH.sub.2).sub.g --;

Wherein g is one, 2, or 3; Wherein R₇ is

    --(CH.sub.2).sub.m --CH.sub.3,

wherein m is one to 5, inclusive; Wherein L₁ is ##STR3## or a mixture of##STR4## wherein R₃ and R₄ are hydrogen, methyl, or fluoro, being thesame or different, with the proviso that one of R₃ and R₄ is methyl onlywhen the other is hydrogen or methyl; Wherein M₁ is ##STR5## wherein R₅and R₆ are hydrogen or methyl, with the proviso that one of R₅ and R₆ ismethyl only when the other is hydrogen; and Wherein R₁ is hydrogen,alkyl of one to 12 carbon atoms, inclusive, cycloalkyl of 3 to 10 carbonatoms, inclusive, aralkyl of 7 to 12 carbon atoms, inclusive, phenyl,phenyl substituted with one, two, or three chloro or alkyl of one to 3carbon atoms, inclusive, or a pharmacologically acceptable cation.
 2. Acompound according to claim 1, wherein D is ##STR6##
 3. A compoundaccording to claim 2, wherein M₁ is ##STR7##
 4. A compound according toclaim 3, wherein g is one.
 5. A compound according to claim 4, whereinR₃, R₄, R₅, and R₆ are all hydrogen. 6.15-epi-5-Oxa-13,14-didehydro-8β,12α-11-deoxy-PGE₁, methyl ester, acompound according to claim
 4. 7. A compound according to claim 2,wherein M₁ is ##STR8##
 8. A compound according to claim 7, wherein g isthree.
 9. A compound according to claim 7, wherein g is one.
 10. Acompound according to claim 9, wherein R₃ and R₄ are both hydrogen. 11.A compound according to claim 10, wherein R₆ is methyl. 12.5-Oxa-13,14-didehydro-8β,12α-11-deoxy-PGE₁, 15-methyl ether, a compoundaccording to claim
 11. 13. 5-Oxa-13,14-didehydro-8β,12α-11 -deoxy-PGE₁,methyl ester, 15-methyl ether, a compound according to claim
 11. 14. Acompound according to claim 10, wherein R₅ and R₆ are both hydrogen. 15.5-Oxa-13,14-didehydro-8β,12α-11-deoxy-PGE₁, a compound according toclaim
 14. 16. 5-Oxa-13,14-didehydro-8β,12α-11-deoxy-PGE₁, methyl ester,a compound according to claim
 14. 17. A compound according to claim 9,wherein at least one of R₃ and R₄ is methyl.
 18. A compound according toclaim 17, wherein R₃ and R₄ are both methyl.
 19. A compound according toclaim 18, wherein R₅ is methyl. 20.5-Oxa-15,16,16-trimethyl-13,14-didehydro-8β,12α-11-deoxy-PGE₁, methylester, a compound according to claim
 19. 21. A compound according toclaim 18, wherein R₆ is methyl. 22.5-Oxa-16,16-dimethyl-13,14-didehydro-8β,12α-11-deoxy-PGE₁, methyl ester,15-methyl ether, a compound according to claim
 21. 23. A compoundaccording to claim 18, wherein R₅ and R₆ are both hydrogen. 24.5-Oxa-16,16-dimethyl-13,14-didehydro-8β,12α-11-deoxy-PGE₁, a compoundaccording to claim
 23. 25.5-Oxa-16,16-dimethyl-13,14-didehydro-8β,12α-11-deoxy-PGE₁, methyl ester,a compound according to claim
 23. 26. A compound according to claim 9,wherein at least one of R₃ and R₄ is fluoro.
 27. A compound according toclaim 26, wherein R₃ and R₄ are both fluoro.
 28. A compound according toclaim 27, wherein R₅ is methyl. 29.5-Oxa-15-methyl-16,16-difluoro-13,14-didehydro-8β,12.alpha.-11-deoxy-PGE₁,methyl ester, a compound according to claim
 28. 30. A compound accordingto claim 27, wherein R₆ is methyl. 31.5-Oxa-16,16-difluoro-13,14-didehydro-8β,12α-11-deoxy-PGE₁, methyl ester,15-methyl ether, a compound according to claim
 30. 32. A compoundaccording to claim 27, wherein R₅ and R₆ are both hydrogen. 33.5-Oxa-16,16-difluoro-13,14-didehydro-8β,12α-11-deoxy-PGE₁, a compoundaccording to claim
 32. 34.5-Oxa-16,16-difluoro-13,14-didehydro-8β,12α-11-deoxy-PGE₁, methyl ester,a compound according to claim
 32. 35. A compound according to claim 1,wherein D is ##STR9##
 36. A compound according to claim 35, wherein M₁is ##STR10##
 37. A compound according to claim 36, wherein g is one. 38.A compound according to claim 37, wherein R₃, R₄, R₅, and R₆ are allhydrogen.
 39. 15-epi-5-Oxa-13,14-didehydro-11-deoxy-PGE₁, methyl ester,a compound according to claim
 38. 40. A compound according to claim 35,wherein M₁ is ##STR11##
 41. A compound according to claim 40, wherein gis three.
 42. A compound according to claim 40, wherein g is one.
 43. Acompound according to claim 42, wherein R₃ and R₄ are both hydrogen. 44.A compound according to claim 43, wherein R₆ is methyl. 45.5-Oxa-13,14-didehydro-11-deoxy-PGE₁, 15-methyl ether, a compoundaccording to claim
 44. 46. 5-Oxa-13,14-didehydro-11-deoxy-PGE₁, methylester, 15-methyl ether, a compound according to claim
 44. 47. A compoundaccording to claim 43, wherein R₅ and R₆ are both hydrogen. 48.5-Oxa-13,14-didehydro-11-deoxy-PGE₁, a compound according to claim 47.49. 5-Oxa-13,14-didehydro-11-deoxy-PGE₁, methyl ester, a compoundaccording to claim
 47. 50. A compound according to claim 42, wherein atleast one of R₃ and R₄ is methyl.
 51. A compound according to claim 50,wherein R₃ and R₄ are both methyl.
 52. A compound according to claim 51,wherein R₅ is methyl. 53.5-Oxa-15,16,16-trimethyl-13,14-didehydro-11-deoxy-PGE₁, methyl ester, acompound according to claim
 52. 54. A compound according to claim 51,wherein R₆ is methyl. 55.5-Oxa-16,16-dimethyl-13,14-didehydro-11-deoxy-PGE₁, methyl ester,15-methyl ether, a compound according to claim
 54. 56. A compoundaccording to claim 51, wherein R₅ and R₆ are both hydrogen. 57.5-Oxa-16,16-dimethyl-13,14-didehydro-11-deoxy-PGE₁, a compound accordingto claim
 56. 58. 5-Oxa-16,16-dimethyl-13,14-didehydro-11-deoxy-PGE₁,methyl ester, a compound according to claim
 56. 59. A compound accordingto claim 42, wherein at least one of R₃ and R₄ is fluoro.
 60. A compoundaccording to claim 59, wherein R₃ and R₄ are both fluoro.
 61. A compoundaccording to claim 60, wherein R₅ is methyl. 62.5-Oxa-15-methyl-16,16-difluoro-13,14-didehydro-PGE₁ 11-deoxy-PGE₁,methyl ester, a compound according to claim
 61. 63. A compound accordingto claim 60, wherein R₆ is methyl. 64.5-Oxa-16,16-difluoro-13,14-didehydro-11-deoxy-PGE₁, methyl ester,15-methyl ether, a compound according to claim
 63. 65. A compoundaccording to claim 60, wherein R₅ and R₆ are both hydrogen. 66.5-Oxa-16,16-difluoro-13,14-didehydro-11-deoxy-PGE₁, a compound accordingto claim
 65. 67. 5-Oxa-16,16-difluoro-13,14-didehydro-11-deoxy-PGE₁,methyl ester, a compound according to claim 65.